Sodium t-butoxide → N-{[3-(Dibenzylamino)oxetan-3-yl]methyl}-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

HRID 540152Notes

Reaction equation

HRID 540152 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][C:22]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:23][C:17]=3[S:16](=[O:32])(=[O:31])[CH2:15][CH2:14]2)[CH:3]=1.[NH2:33][CH2:34][C:35]1([N:39]([CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:38][O:37][CH2:36]1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:47]([N:39]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:35]1([CH2:34][NH:33][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=[C:4]([N:13]3[CH2:19][C:18]4[CH:20]=[CH:21][C:22]([O:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[CH:23][C:17]=4[S:16](=[O:32])(=[O:31])[CH2:15][CH2:14]3)[CH:3]=2)[CH2:36][O:37][CH2:38]1)[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 574158213-(aminomethyl)-N,N-dibenzyloxetan-3-amineHCID 712551874-(4-Chloro-6-methylquinolin-2-yl)-8-phenoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71255779N-{[3-(Dibenzylamino)oxetan-3-yl]methyl}-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amineYield 52.6%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture solution of 4-(4-chloro-6-methylquinolin-2-yl)-8-phenoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (167.0 mg, 0.36 mmol), (3-(aminomethyl)-N,N-dibenzyloxetan-3-amine (609.0 mg, 2.16 mmol), 1,1′-bis(diphenylphosphino)-ferrocenedichloropalladium(II) (15.0 mg, 0.02 mmol), 1,1′-bis(diphenylphosphino)-ferrocene (11.2 mg, 0.02 mmol) and sodium tert-butoxide (75.0 mg, 0.72 mmol) in 1,4-dioxane (2.0 mL) was heated with stirring at 120° C. for 2 hours under microwave irridiation. After being cooled to room temperature, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by ISCO combi-flash chromatography (gradient elution, 20-60% ethyl acetate in petroleum ether) to afford 134.6 mg of the desired product as a light yellow solid (yield was 52.6%). MS obsd. (ESI+) [(M+H)+] 711.

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionthe reaction mixture was extracted with ethyl acetate (100 mL)
  3. washThe organic layer was washed with brine (50 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by ISCO combi-flash chromatography (gradient elution, 20-60% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-c3b9cbd2b00d41d1af029ca60210af3e
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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